The holocentricity in the dioecious nutmeg (Myristica fragrans) is not based on major satellite repeats.

Holocentric species are characterized by the presence of centromeres throughout the length of the chromosomes. We confirmed the holocentricity of the dioecious, small chromosome-size species Myristica fragrans based on the chromosome-wide distribution of the centromere-specific protein KNL1, α-tubulin fibers, and the cell cycle-dependent histone H3 serine 28 phosphorylation (H3S28ph) mark. Each holocentromere is likely composed of, on average, ten centromere units, but none of the identified and in situ hybridized high-copy satellite repeats is centromere-specific. No sex-specific major repeats are present in the high-copy repeat composition of male or female plants, or a significant difference in genome size was detected. Therefore, it is unlikely that M. fragrans possesses heteromorphic sex chromosomes.

Wound healing effect of nutmeg (Myristica fragrans) cream on second-degree burn in animal model.

Second-degree burn, the most common among burn degrees, underscores the importance of timely and proper treatment in influencing prognosis. Nutmeg (Myristica fragrans), renowned for its potent antibacterial and antifungal properties, also serves as an effective antiseptic for open wounds. The aim of this study was to identify the phytochemical constituents of nutmeg essential oil and analyze the wound healing effect of nutmeg cream on second-degree burns in an animal model. An experimental study with a completed randomized design was conducted on Rattus norvegicus strain Wistar rats with second-degree burn. This study had four groups and each group consisting of four rats: B (burn-treated base cream), B+N (burn-treated 3% nutmeg cream), B+SSD (burn-treated silver sulfadiazine (BSS)), and B+N+SSD (burn-treated 3% nutmeg cream and SSD in a 1:1 ratio). The phytochemical analysis of nutmeg essential oil was conducted by gas chromatography and mass spectroscopy (GC-MS). The burn diameter and burn wound healing percentage were measured from day 0 to 18. One-way ANOVA followed by post hoc analysis using the least significant difference (LSD) was employed to analysis the effect. The phytochemical analysis of nutmeg essential oil found that myristicin, terpinene-4-ol, terpinene, safrole and terpinolene were the most abundant putative compounds in nutmeg essential oil. On day 0, the average burn wound diameters were 1.4 cm in all groups and increases were observed in all groups on day 3. The wound diameter decreased until day 18 with the smallest burn wound diameter was found in the B+N group (0.86±0.37 cm), followed by B+SSD (0.93±0.29 cm). The B+SSD group exhibited the highest percentage of burn wound healing (56.80±14.05%), which was significantly different from the base cream (p<0.05). The percentage of burn wound healing in rats given 3% nutmeg cream was 41.88±13.81%, suggesting that nutmeg cream could promote burn wound healing in rats induced by second-degree burns.

Potential Anti-Gouty Arthritis of Citronella Essential Oil and Nutmeg Essential Oil through Reducing Oxidative Stress and Inhibiting PI3K/Akt/mTOR Activation-Induced NLRP3 Activity.

Citronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)-induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU-induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti-gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.

Detection of major psychoactive compounds (safrole, myristicin, and elemicin) of nutmeg in human serum via GC-MS/MS using MonoSpin® extraction: Application in a nutmeg poisoning case.

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.

Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt.

A new phenylpropanoid, myristriol (1), along with 11 known ones were isolated from the seed kernel of Myristica fragrans Houtt. Their chemical structures were clearly elucidated by extensive spectroscopic analysis. In which, the relative configuration of 1 was finally determined as erythro-1 by comparison the NMR data of two synthetic erythro- and threo-diastereoisomers with that of natural 1.

Anti-Proliferative Acyl Phenols and Arylnonanoids from the Fruit Rind of Myristica malabarica Lam.

Phytochemical investigation of the methanol extract of the fruit rind of Myristica malabarica led to the isolation of eight known compounds that were identified as malabaricones A-D, promalabaricones B and C, 1-(2,6-dihydroxyphenyl)tetradecan-1-one, and ericanone by comparison with literature spectroscopic data. The structures of malabaricones A-D, promalabaricone B, and 1-(2,6-dihydroxyphenyl)tetradecan-1-one were confirmed by X-ray crystallography. In vitro assay of the isolated phenols indicated that they exhibited moderate anti-proliferative activity against the A2780 human ovarian cancer cell. Compounds (1, 3, 5, 6 and 7) had the most potent activities, whereas the anti-proliferative activities of compounds 2 and 4 were less potent.

New Monoterpene-Conjugated Phenolic Constituents from Nutmeg and Their Autophagy Modulating Activities.

The seed of Myristica fragrans Houtt (nutmeg) is one of the important spices that have been extensively used in the culinary, food, beverage, and also in medicinal products industry. Previous phytochemical studies on nutmeg were mainly focused on lignans and neolignans. However, the other constituents have been poorly studied. In this study, 11 new monoterpene-conjugated phenolic derivatives, named myrifratins A-K (1-11), and five known compounds were isolated from nutmeg. The novel neolignan-diarylnonanoid-monoterpene conjugates (1 and 2) were first isolated in nature. Compounds 3-7 were rarely monoterpene-diarylnonanoid-conjugated derivatives, and 8-11 were the first examples of monoterpene-neolignan conjugates. Compounds 4-6, 12, and 13 showed potent autophagy inhibitory activities in a concentration-dependent manner. Our findings showed an uncommon class of monoterpene-conjugated phenolic derivatives in nature and reported their autophagy inhibition activities for the first time, which may give a new insight into the benefits or safety of nutmeg in foods.

Nutmeg (Myristica fragrans Houtt.) essential oil: A review on its composition, biological, and pharmacological activities.

Myristica fragrans (Houtt.) is an evergreen tree native to the Maluku Islands, Indonesia. M. fragrans kernel is extensively used in Indian traditional medicines to treat various diseases. Several studies attempt to compile and interpret the pharmacological potential of Myristica fragrans (Houtt.) aqueous and various chemical extracts. Thus, the pharmacological potential of nutmeg essential oil has not been reviewed phytochemically and pharmacologically. Therefore, the present study aimed to share appropriate literature evidence regarding the plant essential oil chemical composition and therapeutic potential of Myristica fragrans essential oil (MFEO). MFEO of leaf, mace, kernel, and seed were used worldwide as potential Ayurvedic medicine and fragrance. MFEO extracted by various methods and oil yield was 0.7-3.2, 8.1-10.3, 0.3-12.5, and 6.2-7.6% in leaf, mace, seed, and kernel. The primary chemical constituents of MFEO were sabinene, eugenol, myristicin, caryophyllene, ß-myrcene, and α-pinene. Clinical and experimental investigations have confirmed the antioxidant, antimicrobial, antiinflammatory, anticancer, antimalarial, anticonvulsant, hepatoprotective, antiparasitic, insecticidal, and nematocidal activities of MFEO. It is the first attempt to compile oil yield, composition, and the biological activities of MFEO. In future, several scientific investigations are required to understand the mechanism of action of MFEO and their bioactive constituents.

Neolignans from Myristica fragrans seeds, revision of their absolute configurations, reduction products and biological activities.

Chromatographic purification of the CH2Cl2 extract of Myristica fragrans seeds provided 19 known compounds, four dihydrofuran neolignans, licarines A, B and maceneolignans A, B were among the isolates. Prior to hydrogenation, in order to obtain their di- and tetrahydrogenated products, the absolute configuration of these compounds was thoroughly investigated based on their optical rotations and ECD spectra. This report provides evidences concerning the disagreement between the use of an aromatic quadrant rule and time-dependent density function theory calculation for the prediction of the absolute configurations at C-7 and C-8 in these dihydrobenzofuran neolignans. The absolute configurations of licarines A, B and maceneolignans A, B were subsequently redefined. The antimicrobial and cytotoxic activities of the isolates and reduction products of licarines A, B and maceneolignans A, B were also investigated.

Antifungal, Antibacterial, and Cytotoxic Activities of Silver Nanoparticles Synthesized from Aqueous Extracts of Mace-Arils of Myristica fragrans.

In the present study, mace-mediated silver nanoparticles (mace-AgNPs) were synthesized, characterized, and evaluated against an array of pathogenic microorganisms. Mace, the arils of Myristica fragrans, are a rich source of several bioactive compounds, including polyphenols and aromatic compounds. During nano synthesis, the bioactive compounds in mace aqueous extracts serve as excellent bio reductants, stabilizers, and capping agents. The UV-VIS spectroscopy of the synthesized NPs showed an intense and broad SPR absorption peak at 456 nm. Dynamic light scattering (DLS) analysis showed the size with a Z average of 50 nm, while transmission electron microscopy (TEM) studies depicted the round shape and small size of the NPs, which ranged between 5-28 nm. The peaks related to important functional groups, such as phenols, alcohols, carbonyl groups, amides, alkanes and alkenes, were obtained on a Fourier-transform infrared spectroscopy (FTIR) spectrum. The peak at 3 keV on the energy dispersive X-ray spectrum (EDX) validated the presence of silver (Ag). Mace-silver nanoparticles exhibited potent antifungal and antibacterial activity against several pathogenic microorganisms. Additionally, the synthesized mace-AgNPs displayed an excellent cytotoxic effect against the human cervical cancer cell line. The mace-AgNPs demonstrated robust antibacterial, antifungal, and cytotoxic activity, indicating that the mace-AgNPs might be used in the agrochemical industry, pharmaceutical industry, and biomedical applications. However, future studies to understand its mode of action are needed.

Pharmacological and Therapeutic Potential of Myristicin: A Literature Review.

Natural products have been used by humanity for many centuries to treat various illnesses and with the advancement of technology, it became possible to isolate the substances responsible for the beneficial effects of these products, as well as to understand their mechanisms. In this context, myristicin, a substance of natural origin, has shown several promising activities in a large number of in vitro and in vivo studies carried out. This molecule is found in plants such as nutmeg, parsley, carrots, peppers, and several species endemic to the Asian continent. The purpose of this review article is to discuss data published in the last 10 years at Pubmed, Lilacs and Scielo databases, reporting beneficial effects, toxicity and promising data of myristicin for its future use in medicine. From 94 articles found in the literature, 68 were included. Exclusion criteria took into account articles whose tested extracts did not have myristicin as one of the major compounds.

Effect of the essential oils of Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus S. on mycotoxin-producing Aspergillus flavus and Aspergillus ochraceus antifungal properties of essential oils.

Essential oils can be a useful alternative to the use of synthetic fungicides because they have biological potential and are relatively safe for food and agricultural products. The objectives of the present study were to evaluate the antifungal and antimycotoxigenic activities of the essential oils from Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus S. against Aspergillus flavus and Aspergillus ochraceus, as well as their effects on ergosterol synthesis and membrane morphology. The antifungal potential was evaluated by mycelial growth analysis and scanning electron microscopy. Fungicidal effects against A. flavus, with MFC of 0.98, 15.62 and 0.98 µL/mL, respectively, were observed for the essential oils from S. montana, M. fragrans and C. flexuosus. Aspergillus ochraceus did not grow in the presence of concentrations of 3.91, 15.62 and 0.98 µL/mL of the essential oils from S. montana, M. fragrans and C. flexuosus, respectively. The essential oils significantly inhibited the production of ochratoxin A by the fungus A. ochraceus. The essential oils also inhibited the production of aflatoxin B1 and aflatoxin B2. The biosynthesis of ergosterol was inhibited by the applied treatments. Biological activity in the fungal cell membrane was observed in the presence of essential oils, given that deleterious effects on the morphologies of the fungi were detected. The essential oils under study are promising as food preservatives because they significantly inhibit toxigenic fungi that contaminate food. In addition, the essential oils hindered the biosynthesis of mycotoxins.

Comparison of antifungal activity of selected essential oils against Fusarium graminearum in vitro.

INTRODUCTION: Fusaria are microscopic filamentous fungi which are spread in soil, in various organic substrates, and include more than 80 phytopathogenic species which are predominantly hosted by cereals, fruits and vegetables. Many of these species, under certain conditions, are capable of synthesizing secondary metabolites, mycotoxins. At present, various substances are used for their elimination and one of the solutions appears to be essential oils. In the presented study, the antifungal activity of essential oils was researched in vitro. MATERIAL AND METHODS: In this study, two standard fungal isolates Fusarium graminearum CCM F-683 and Fusarium graminearum CCM 8244 (Brno, Czech Republic) were used. The antifungal effect of 6 tested essential oils (Syzygium aromaticum, Origanum vulgare, Thymus vulgaris, Hyssopus officinalis , Ocimum basilicum, Myristica fragrans) was determined using the broth microdilution method, which allows reading of the MIC (minimum inhibitory concentration). According to the results obtained, the growth inhibition of Fusarium graminearum was determined by assay for the inhibition of radial growth of the mycelium. RESULTS: The inhibitory effects of thymus, oregano, basil, myristica, hyssop and syzygium essential oil (EO) on mycelial growth of Fusarium graminearum CCM F-683 and CCM 8244 were investigated. The best antifungal activity against the both strains of Fusarium graminearum (37.4%; 40.7%) was demonstrated by Origanum vulgare EO at the concentration 100 µg/mL. Among the four tested oils, three (Syzygium aromaticum, Thymus vulgaris, Origanum vulgare) achieved the best inhibitory effect (100%) at concentrations 500 µg/mL and 1000 µg/mL. CONCLUSIONS: In the protection of plants against pathogenic fungi, essential oils appear to be a suitable substitute for synthetic chemicals.

Inhibition of Bacterial Efflux Pumps by Crude Extracts and Essential Oil from Myristica fragrans Houtt. (Nutmeg) Seeds against Methicillin-Resistant Staphylococcus aureus.

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment.

Application and safety evaluation of an anti-aflatoxigenic chitosan pouch containing turmeric essential oil in the storage of traditional Chinese health food.

Aflatoxin contamination is one of the most important factors jeopardizing the quality of traditional Chinese health food (TCHF) during storage. Based on our previous work, we investigated the stability of chitosan (CH) films containing turmeric essential oil (TEO) and employed CH-TEO films as inner pouches, then stored them with inoculated Coix seed, nutmeg, and Ziziphi Spinosae Semen (ZSS). We found that the stability of CH-TEO was most affected by high temperature, and these pouches dramatically decreased aflatoxin accumulation and maintained levels of marker components of each TCHF. We found that glycerol tristearat in Coix seed and jujuboside A and spinosin in ZSS were negatively correlated with aflatoxin accumulation. After three months of storage with a CH-TEO pouch, we found little change in marker components contents, but observed that Coix seed had the relative lower sensory characteristics score. In addition, acute and 90-day subchronic toxicity test in Coix seed stored with the largest amount of TEO showed no significant signs of toxicity or treatment-related changes in animals. The present study is the first report on the study of a green, efficient, and low toxicity solution for aflatoxic contamination in TCHF, and provides strong support for its future use.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King.

The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 µM) and potent (7.55 ± 1.64 µM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Nutmegs and wild nutmegs: An update on ethnomedicines, phytochemicals, pharmacology, and toxicity of the Myristicaceae species.

Prized medicinal spice true nutmeg is obtained from Myristica fragrans Houtt. Rest species of the family Myristicaceae are known as wild nutmegs. Nutmegs and wild nutmegs are a rich reservoir of bioactive molecules and used in traditional medicines of Europe, Asia, Africa, America against madness, convulsion, cancer, skin infection, malaria, diarrhea, rheumatism, asthma, cough, cold, as stimulant, tonics, and psychotomimetic agents. Nutmegs are cultivated around the tropics for high-value commercial spice, used in global cuisine. A thorough literature survey of peer-reviewed publications, scientific online databases, authentic webpages, and regulatory guidelines found major phytochemicals namely, terpenes, fatty acids, phenylpropanoids, alkanes, lignans, flavonoids, coumarins, and indole alkaloids. Scientific names, synonyms were verified with www.theplantlist.org. Pharmacological evaluation of extracts and isolated biomarkers showed cholinesterase inhibitory, anxiolytic, neuroprotective, anti-inflammatory, immunomodulatory, antinociceptive, anticancer, antimicrobial, antiprotozoal, antidiabetic, antidiarrhoeal activities, and toxicity through in-vitro, in-vivo studies. Human clinical trials were very few. Most of the pharmacological studies were not conducted as per current guidelines of natural products to ensure repeatability, safety, and translational use in human therapeutics. Rigorous pharmacological evaluation and randomized double-blind clinical trials are recommended to analyze the efficacy and therapeutic potential of nutmeg and wild nutmegs in anxiety, Alzheimer's disease, autism, schizophrenia, stroke, cancer, and others.

Comparing the efficacy of nutmeg essential oil and a chemical pesticide against Musca domestica and Chrysomya albiceps for selecting a new insecticide agent against synantropic vectors.

The insecticidal activity of Myristica fragrans (Houtt) essential seed oil, (Nutmeg) was evaluated against Musca domestica (Linnaeus) and Chrysomya albiceps (Wiedemann); both important infectious pathogenic disease vectors. The oil was extracted by distillation, and 21 components were identified during chemical analysis; principally ß-pinene (26%), α-pinene (10.5%), Sabinene (9.1%) and γ-terpinen (8.5%). Insecticidal properties were identified through larvicide and adulticide tests. Using the immersion method, the oil at 5% was found to be very effective (90 ± 1%) against M. domestica larvae. The results for adulticide activity varied by fly species, dosage, time, and method of exposure. Topical application (on the insect thorax) was more toxic to C. albiceps, where the lethal concentration at 50% (LC50) was 2.02 ± 0.56, and 8.57 ± 2.41 for the common flies. When the insects were exposed to oil impregnated paper, the results were similar for M. domestica and C. albiceps adults with respective LC50 values of 2.74 ± 0.24, and 3.65 ± 0.48. Thus, the results demonstrated that M. fragrans oil presents insecticidal activity and can be used for control of Musca domestica and Chrysomya albiceps.

Abuse of nutmeg seeds: Detectable by means of liquid chromatography-mass spectrometry techniques?

Numerous case reports of intoxications with nutmeg seeds (Myristica fragrans, Houtt.) can be found in literature often following their abuse, as psychotropic effects were described after ingestions of large doses. The successful detection of the main ingredients of the nutmeg seeds essential oil elemicin, myristicin, and safrole, as well as their metabolites in human urine by gas chromatography coupled to mass spectrometry (GC-MS) was already described. The aim of this study was to investigate the detectability of the main ingredients of nutmeg seeds and their metabolites in human blood and urine samples using liquid chromatography coupled to linear ion trap mass spectrometry (LC-LIT-MSn ) and liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) after nutmeg seed abuse. Sample material of three individuals was retrospectively investigated after a systematic screening approach indicated an intoxication with nutmeg seeds as a likely cause of symptoms. Metabolic patterns in plasma and urine using GC-MS were comparable with those described in earlier publications. Investigations using hyphenated liquid chromatography techniques lead to the detection of myristicin and safrole, as well as further metabolites not described using GC-MS and revealed sulfation as an additional Phase II metabolic pathway. These results might help to detect or confirm future intoxications with nutmeg seeds by using LC-MS techniques.

The effect of nutmeg essential oil constituents on Novikoff hepatoma cell viability and communication through Cx43 gap junctions.

Essential oils from plants are a potential source of molecules having anti-inflammatory, anticancer, cardiotropic, and other activities. However, most of these effects lack mechanistic explanations and structure-activity relationship testing. In the present study, we: 1) identified the nutmeg essential oil (NEO) composition; 2) using molecular docking, we determined the putative regulatory binding sites on the connexin 43 (Cx43) that is responsible for gap junction-dependent intercellular communication (GJIC) in the majority of tissues; 3) examined the effect of NEO and its three constituents - sabinene, α-pinene, and α-copaene - on GJ conductance and gating in Novikoff cells expressing endogenous Cx43; and 4) verified whether NEO effects on GJIC correlated with its action on Novikoff cell viability, proliferation, and colony formation capability. Our results revealed NEO and its constituents as potent and efficient Cx43 GJ inhibitors acting by slow gating mechanism. In addition, NEO reduced Novikoff hepatoma cell viability, proliferation, and colony formation capability; however, this was achieved at higher doses and was unrelated to its effects on GJIC.